PMID- 30891496
OWN - NLM
STAT- MEDLINE
DCOM- 20200424
LR  - 20200424
IS  - 2375-2548 (Electronic)
IS  - 2375-2548 (Linking)
VI  - 5
IP  - 3
DP  - 2019 Mar
TI  - Human pluripotent stem cell-derived brain pericyte-like cells induce blood-brain 
      barrier properties.
PG  - eaau7375
LID - 10.1126/sciadv.aau7375 [doi]
LID - eaau7375
AB  - Brain pericytes play important roles in the formation and maintenance of the 
      neurovascular unit (NVU), and their dysfunction has been implicated in central 
      nervous system disorders. While human pluripotent stem cells (hPSCs) have been 
      used to model other NVU cell types, including brain microvascular endothelial 
      cells (BMECs), astrocytes, and neurons, hPSC-derived brain pericyte-like cells 
      have not been integrated into these models. In this study, we generated neural 
      crest stem cells (NCSCs), the embryonic precursor to forebrain pericytes, from 
      hPSCs and subsequently differentiated NCSCs to brain pericyte-like cells. These 
      cells closely resembled primary human brain pericytes and self-assembled with 
      endothelial cells. The brain pericyte-like cells induced blood-brain barrier 
      properties in BMECs, including barrier enhancement and reduced transcytosis. 
      Last, brain pericyte-like cells were incorporated with iPSC-derived BMECs, 
      astrocytes, and neurons to form an isogenic human model that should prove useful 
      for the study of the NVU.
FAU - Stebbins, Matthew J
AU  - Stebbins MJ
AUID- ORCID: 0000-0003-1591-7295
AD  - Department of Chemical and Biological Engineering, University of 
      Wisconsin-Madison, Madison, WI, USA.
FAU - Gastfriend, Benjamin D
AU  - Gastfriend BD
AD  - Department of Chemical and Biological Engineering, University of 
      Wisconsin-Madison, Madison, WI, USA.
FAU - Canfield, Scott G
AU  - Canfield SG
AUID- ORCID: 0000-0003-1328-7365
AD  - Department of Chemical and Biological Engineering, University of 
      Wisconsin-Madison, Madison, WI, USA.
FAU - Lee, Ming-Song
AU  - Lee MS
AD  - Department of Orthopedics and Rehabilitation, University of Wisconsin School of 
      Medicine and Public Health, Madison, WI, USA.
FAU - Richards, Drew
AU  - Richards D
AUID- ORCID: 0000-0002-9366-2833
AD  - Department of Chemical and Biological Engineering, University of 
      Wisconsin-Madison, Madison, WI, USA.
FAU - Faubion, Madeline G
AU  - Faubion MG
AD  - Department of Chemical and Biological Engineering, University of 
      Wisconsin-Madison, Madison, WI, USA.
FAU - Li, Wan-Ju
AU  - Li WJ
AD  - Department of Orthopedics and Rehabilitation, University of Wisconsin School of 
      Medicine and Public Health, Madison, WI, USA.
FAU - Daneman, Richard
AU  - Daneman R
AD  - Departments of Neuroscience and Pharmacology, University of California, San 
      Diego, San Diego, CA, USA.
FAU - Palecek, Sean P
AU  - Palecek SP
AUID- ORCID: 0000-0003-4917-5584
AD  - Department of Chemical and Biological Engineering, University of 
      Wisconsin-Madison, Madison, WI, USA.
FAU - Shusta, Eric V
AU  - Shusta EV
AUID- ORCID: 0000-0002-4297-0158
AD  - Department of Chemical and Biological Engineering, University of 
      Wisconsin-Madison, Madison, WI, USA.
LA  - eng
GR  - R01 NS083688/NS/NINDS NIH HHS/United States
GR  - R01 NS103844/NS/NINDS NIH HHS/United States
GR  - T32 GM008349/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20190313
PL  - United States
TA  - Sci Adv
JT  - Science advances
JID - 101653440
RN  - 0 (Antigens)
RN  - 0 (Biomarkers)
RN  - 0 (NGFR protein, human)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (Proteoglycans)
RN  - 0 (Receptors, Nerve Growth Factor)
RN  - 0 (chondroitin sulfate proteoglycan 4)
RN  - EC 2.7.10.1 (PDGFRB protein, human)
RN  - EC 2.7.10.1 (Receptor, Platelet-Derived Growth Factor beta)
SB  - IM
MH  - Animals
MH  - Antigens/genetics/metabolism
MH  - Astrocytes/cytology/metabolism
MH  - Biomarkers/metabolism
MH  - Blood-Brain Barrier/*metabolism
MH  - Cell Differentiation
MH  - Coculture Techniques
MH  - Endothelial Cells/cytology/*metabolism
MH  - Gene Expression
MH  - Humans
MH  - Induced Pluripotent Stem Cells/cytology/*metabolism
MH  - Male
MH  - Nerve Tissue Proteins/genetics/metabolism
MH  - Neural Crest/cytology/*metabolism
MH  - Neurons/cytology/metabolism
MH  - Pericytes/cytology/*metabolism
MH  - Primary Cell Culture
MH  - Prosencephalon/cytology/growth & development/metabolism
MH  - Proteoglycans/genetics/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptor, Platelet-Derived Growth Factor beta/genetics/metabolism
MH  - Receptors, Nerve Growth Factor/genetics/metabolism
MH  - Transcytosis/*genetics
PMC - PMC6415958
EDAT- 2019/03/21 06:00
MHDA- 2020/04/25 06:00
PMCR- 2019/03/13
CRDT- 2019/03/21 06:00
PHST- 2018/07/11 00:00 [received]
PHST- 2019/01/29 00:00 [accepted]
PHST- 2019/03/21 06:00 [entrez]
PHST- 2019/03/21 06:00 [pubmed]
PHST- 2020/04/25 06:00 [medline]
PHST- 2019/03/13 00:00 [pmc-release]
AID - aau7375 [pii]
AID - 10.1126/sciadv.aau7375 [doi]
PST - epublish
SO  - Sci Adv. 2019 Mar 13;5(3):eaau7375. doi: 10.1126/sciadv.aau7375. eCollection 2019 
      Mar.